The value of biomarkers in patients with sarcomatoid carcinoma of the lung: molecular analysis of 33 cases

Clin Lung Cancer. 2012 Jul;13(4):288-96. doi: 10.1016/j.cllc.2011.11.004. Epub 2011 Dec 13.

Abstract

To better understand the prognosis of sarcomatoid carcinoma of the lung, the correlation between several biomarkers (ERCC1 [excision repair cross-complementation group 1] and EGFR [epidermal growth factor receptor] expression, EGFR and KRAS mutations, and EGFR copy number) and clinical outcomes in 33 patients with lung sarcomatoid carcinoma was evaluated. Survival analysis identified several significant factors that predicted overall survival.

Background: Sarcomatoid carcinoma (SC) of the lung is a rare histologic group of lung cancers with a poor prognosis. To better understand the prognosis of lung SC, in this study, we evaluated the correlation between several biomarkers and clinical outcomes in patients with lung SC.

Patients and methods: A cohort of 33 patients with lung SC was studied. Protein expressions of excision repair cross-complementation group 1 (ERCC1) and epidermal growth factor receptor (EGFR) were examined by immunohistochemistry. Somatic EGFR and KRAS mutations were identified by direct sequencing. EGFR gene copy number was evaluated by fluorescence in situ hybridization. ERCC1 messenger RNA expression in paraffin-embedded tumor specimens was detected by branched DNA assay.

Results: Our analyses identified 9 patients (9/32) with EGFR mutations and only 1 patient (1/32) with a KRAS mutation. No exon 19 deletion of EGFR gene was detected. Lower messenger RNA levels of ERCC1 were detected in patients with EGFR mutations and/or fluorescence in situ hybridization amplified status. Survival analysis identified several significant factors, including performance status and clinical staging, that predicted for overall survival.

Conclusion: SC exhibits diverse genotypic variations. Results of our study suggest that chemotherapy could still be an optimal solution for untreated advanced SC, whereas EGFR tyrosine kinase domain inhibitors alone may not be an effective approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Giant Cell / genetics
  • Carcinoma, Giant Cell / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinosarcoma / genetics
  • Carcinosarcoma / metabolism
  • Cohort Studies
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, erbB-1 / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • Pulmonary Blastoma / genetics
  • Pulmonary Blastoma / metabolism
  • RNA, Messenger / analysis
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • EGFR protein, human
  • ErbB Receptors
  • ERCC1 protein, human
  • Endonucleases
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins